期刊
EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS
卷 71, 期 2, 页码 303-309出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.ejpb.2008.09.005
关键词
Plasmid DNA; Cationic lipids; Lipoplexes; Cytokine; Liver injury
资金
- Ministry of Education, Culture, Sports, Science, and Technology of Japan
- Ministry of Health, Labour and Welfare of Japan
- Radioisotope Research Center of Kyoto University
The purpose of this study was to investigate the cytokine production and liver injury induced by lipoplexes prepared with DOTMA/cholesterol and DOTAP/cholesterol liposomes with various mixing ratios in mice. Lipoplexes were prepared with pCMV-Luc and DOTMA/cholesterol or DOTAP/cholesterol lipocomes. After intravenous administration into the mice, organ luciferase activity and serum TNF alpha and ALT were measured to evaluate the transfection efficacy, cytokine production and liver injury. After intravenous administration of these lipoplexes, basically the serum TNR alpha and ALT levels were in agreement with the transfection efficacy of the lipoplexes. The cytokine production and liver injury were markedly suppressed by reducing the pDNA dose, and achieved normal levels at a pDNA close of 0.47 mg/kg. As far as the effects of the charge ratio at this low pDNA dose are concerned, the charge ratios of the lipoplexes affected the transfection efficacy, but not the cytokine production and liver injury. After intravenous administration of either DOTAP/cholesterol or DOTMA/cholesterol liposomes, serum TNF alpha and ALT levels were normal, suggesting that liver injury as well as cytokine production was caused by lipoplexes, but not by cationic liposomes. This information will be valuable for the future optimization of the preparation conditions of lipoplexes for use in clinical gene therapy. (C) 2008 Elsevier B.V. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据